Abstract
Control of the intracellular levels of phosphatidylinositol-(3, 4, 5)-trisphosphate by PI3K and phosphatase and tensin homolog (PTEN) is essential for B cell development and differentiation. Deletion of the PI3K catalytic subunit p110delta leads to a severe reduction in B1 and marginal zone (MZ) B cells, whereas deletion of PTEN results in their expansion. We have examined the relationship between these two molecules by generating mice with a B cell-specific deletion of PTEN (PTENB) and a concurrent germline deletion of p110delta. The expanded B1 cell population of PTENB mice was reduced to normal levels in PTENB/p110delta mutant mice, indicating a critical role for the p110delta isoform in the expansion of B1 cells. However, numbers of MZ B cells in the PTENB/p110delta mutants was intermediate between wild-type and PTENB-deficient mice, suggesting an additional role for other PI3K catalytic isoforms in MZ differentiation. Furthermore, the defective class switch recombination in PTENB B cells was only partially reversed in PTENB/p110delta double mutant B cells. These results demonstrate an epistatic relationship between p110delta and PTEN. In addition, they also suggest that additional PI3K catalytic subunits contribute to B cell development and function.
Original language | English |
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Pages (from-to) | 739-46 |
Number of pages | 8 |
Journal | Journal of Immunology |
Volume | 180 |
Issue number | 2 |
Publication status | Published - 15 Jan 2008 |
Keywords
- Animals
- PTEN Phosphohydrolase
- Transgenes
- Proto-Oncogene Proteins c-akt
- Immunoglobulin Class Switching
- Mice
- B-Lymphocytes
- Mice, Transgenic
- Phosphatidylinositol 3-Kinases
- Protein Isoforms
- Gene Deletion
- Lymphocyte Activation
- Phenotype
- Proto-Oncogene Proteins c-bcl-2
- Mice, Mutant Strains
- Phosphorylation
- Recombination, Genetic